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1.
Anal Bioanal Chem ; 404(5): 1317-26, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22543714

RESUMO

This paper discusses gene expression changes in the skin of mice treated by monoenergetic 14 MeV neutron irradiation and the possibility of monitoring the resultant lipid depletion (cross-validated by functional genomic analysis) as a marker of radiation exposure by high-resolution FT-IR (Fourier transform infrared) imaging spectroscopy. The irradiation was performed at the ENEA Frascati Neutron Generator (FNG), which is specifically dedicated to biological samples. FNG is a linear electrostatic accelerator that produces up to 1.0 × 10(11) 14-MeV neutrons per second via the D-T nuclear reaction. The functional genomic approach was applied to four animals for each experimental condition (unirradiated, 0.2 Gy irradiation, or 1 Gy irradiation) 6 hours or 24 hours after exposure. Coregulation of a subclass of keratin and keratin-associated protein genes that are physically clustered in the mouse genome and functionally related to skin and hair follicle proliferation and differentiation was observed. Most of these genes are transiently upregulated at 6 h after the delivery of the lower dose delivered, and drastically downregulated at 24 h after the delivery of the dose of 1 Gy. In contrast, the gene coding for the leptin protein was consistently upregulated upon irradiation with both doses. Leptin is a key protein that regulates lipid accumulation in tissues, and its absence provokes obesity. The tissue analysis was performed by monitoring the accumulation and the distribution of skin lipids using FT-IR imaging spectroscopy. The overall picture indicates the differential modulation of key genes during epidermis homeostasis that leads to the activation of a self-renewal process at low doses of irradiation.


Assuntos
Leptina/metabolismo , Nêutrons , Pele/metabolismo , Pele/efeitos da radiação , Espectroscopia de Infravermelho com Transformada de Fourier , Animais , Leptina/análise , Metabolismo dos Lipídeos , Lipídeos/análise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doses de Radiação
2.
Curr Cancer Drug Targets ; 9(2): 118-30, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19275753

RESUMO

The natural polyamines (PA), putrescine (PUT), spermidine (SPD) and spermine (SPM) are ubiquitous constituents of eukaryotic cells. The increase of PA in malignant and proliferating cells attracted the interest of scientists during last decades, addressing PA depletion as a new strategy to inhibit cell growth. Selective enzyme inhibitors were developed for decreasing PA metabolism and to act as chemotherapeutic anticancer agents. Indeed, the complexity of the PA homoeostasis overcomes the PA perturbation by a single enzyme to take effect therapeutically. Recently, an increasing interest has been posed on spermine-oxidase (SMO), the only catabolic enzyme able to specifically oxidise SPM. Interestingly, the absence of SPM is compatible with life, but its accumulation and degradation is lethal. Augmented SMO activity provokes an oxidative stress rendering cells prone to die, and appears to be important in the cell differentiation pathway. Extra-cellular SPM is cytotoxic, but its analogues are capable of inhibiting cell growth at low concentrations, most likely by intracellular SPM depletion. These pivotal roles seem to evoke the biological processes of stress response, wherein balance is mandatory to live or to die. Thus, altering SPM metabolism could allow a multi-tasking therapeutic strategy, addressed not only to inhibit PA metabolism. Several tetramines are presently in early phases (I and II) of clinical trials, and it will be a matter of a few more years to understand whether SPM-related therapeutic approaches would be of benefit for composite treatment protocols of cancer.


Assuntos
Antineoplásicos/farmacologia , Espermina/antagonistas & inibidores , Espermina/metabolismo , Animais , Poliaminas Biogênicas/metabolismo , Inibidores Enzimáticos/farmacologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Humanos , Inflamação/fisiopatologia , Modelos Moleculares , Neoplasias/tratamento farmacológico , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/antagonistas & inibidores , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Conformação Proteica , Espermina/análogos & derivados
3.
Biochim Biophys Acta ; 1773(6): 774-83, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17363080

RESUMO

In the aging process and in most degenerative diseases, the oxidant by-products of cellular metabolism lead to oxidative stress. Oxidative stress plays an important role in switching from cell proliferation to its opposite outcome, cell death. The metabolic pathways in charge of the interconversion and degradation of the polyamines are responsible for oxidant by-products. In the past few years, spermine metabolism has been found closely related to DNA oxidation and apoptosis. Moreover, that the ectopical expression of murine spermine oxidase induced DNA damage in the neuroblastoma cell line, and this was uncoupled with any increase in cell mortality, thus suggests an activation of DNA repair. In this work, we provide new evidence showing that only spermine oxidase overactivity can deliver sub-lethal chronic DNA damage and repair without affecting transcriptional and enzymatic levels of the PA key regulatory enzymes ODC and SSAT. Chronic sub-lethal DNA damage is below the cell cycle arrest induction threshold, but is able to activate apurinic/apyrimidinic endonuclease protein (APE1) and gamma H2AX. Of therapeutic interest, the chronic sub-lethal DNA damage and activation of the repair processes are in turn responsible for inducing hypersensitivity after exposure to radiation with no induction of adaptive response to damage.


Assuntos
Proliferação de Células/efeitos da radiação , Dano ao DNA/efeitos da radiação , Reparo do DNA/efeitos da radiação , Estresse Oxidativo/efeitos da radiação , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/biossíntese , Raios X , Envelhecimento/metabolismo , Envelhecimento/efeitos da radiação , Animais , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Dano ao DNA/genética , Reparo do DNA/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Histonas/metabolismo , Camundongos , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética
4.
Prensa méd. argent ; 92(10): 657-665, dic. 2005. tab
Artigo em Espanhol | LILACS | ID: lil-427093

RESUMO

Hemos planteado el presente trabajo, teniendo en cuenta los siguientes aspectos: describir las características epidemiológicas y demográficas en la población estudiada y además caracterizar especialmente los factores higiénicos, sanitarios y culturales que por su heterogeneidad, tuvieron influencia en la capacidad de infección por el Helicobacter Pylori


Assuntos
Adolescente , Adulto , Humanos , Idoso , Demografia , Escolaridade , Estudos Epidemiológicos , Indicadores Básicos de Saúde , Helicobacter pylori , Indicadores Econômicos/estatística & dados numéricos , Qualidade de Vida , Classe Social
5.
Prensa méd. argent ; 92(10): 657-665, dic. 2005. tab
Artigo em Espanhol | BINACIS | ID: bin-411

RESUMO

Hemos planteado el presente trabajo, teniendo en cuenta los siguientes aspectos: describir las características epidemiológicas y demográficas en la población estudiada y además caracterizar especialmente los factores higiénicos, sanitarios y culturales que por su heterogeneidad, tuvieron influencia en la capacidad de infección por el Helicobacter Pylori


Assuntos
Adolescente , Adulto , Humanos , Idoso , Helicobacter pylori/classificação , Estudos Epidemiológicos , Qualidade de Vida , Classe Social , Indicadores Econômicos/estatística & dados numéricos , Indicadores Básicos de Saúde , Qualidade de Vida , Escolaridade , Demografia
6.
Biochim Biophys Acta ; 1755(1): 15-24, 2005 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-15907589

RESUMO

In mammals, the polyamines affect cell growth, differentiation, and apoptosis; their levels are increased in malignant and proliferating cells, thus justifying an interest in a chemotherapeutic approach to cancer. The flavoprotein SMO is the most recently characterized catabolic enzyme, preferentially oxidizing SPM to SPD, 3-aminopropanal and H(2)O(2). In this report, we describe a novel functional characterization of the recently cloned splice variant isoforms from mouse brain, encoding, among others, the nuclear co-localized spermine oxidase mSMOmu. The over-expression of the active isoforms mSMOalpha and mSMOmu, and the inactive mSMOdelta and mSMOgamma in mouse neuroblastoma cells, demonstrated the first evidence of the direct oxidative DNA damage by the SMO activities, either alone or, in a higher extent, when associated with radiation exposure, thus working as radio sensitizer. These effects were reverted by treatment with 50 muM and 100 muM doses of the inhibitor of SMO activity MDL 72,527. The over-expression of all SMO isoforms failed to influence the expression of the regulating enzymes of polyamines metabolism ODC and SSAT. Dealing with the unbalanced tissue specific SMO activities, these results could indicate a new direction to tailor chemotherapy-associated radiotherapy, improving dose-rate protocol and allowing the modulation of deleterious side effects on healthy tissues.


Assuntos
Apoptose , Dano ao DNA , Guanina/análogos & derivados , Neuroblastoma/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo , Tolerância a Radiação , Animais , Guanina/metabolismo , Isoenzimas/metabolismo , Camundongos , Oxirredução , Poliaminas/metabolismo , Células Tumorais Cultivadas
7.
Acta Gastroenterol Latinoam ; 33(4): 199-203, 2003.
Artigo em Espanhol | MEDLINE | ID: mdl-14708472

RESUMO

OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24-h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0, basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then "wash out" for 7 days and thereafter 7 more days' therapy with PZ or OZ. On day 22 a 24-h intragastric pH control was performed again. In the last treatment stage, all of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL 22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57 +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001. Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4) 0.65. CONCLUSIONS: According to the results it might be stated that both proton pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is more effective than pantoprazole as acid-supressor, with statistically significative differences. There was no difference between 20 mg omeprazole and 40 mg pantoprazole.


Assuntos
Antiulcerosos/farmacologia , Benzimidazóis/farmacologia , Ácido Gástrico/metabolismo , Omeprazol/farmacologia , Inibidores da Bomba de Prótons , Sulfóxidos/farmacologia , 2-Piridinilmetilsulfinilbenzimidazóis , Adulto , Análise de Variância , Estudos Cross-Over , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Pantoprazol , Fatores de Tempo
8.
Acta gastroenterol. latinoam ; 33(4): 199-203, 2003. tab
Artigo em Espanhol | LILACS | ID: lil-359984

RESUMO

OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24-h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0, basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then "wash out" for 7 days and thereafter 7 more days' therapy with PZ or OZ. On day 22 a 24-h intragastric pH control was performed again. In the last treatment stage, all of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL 22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57 +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001. Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4) 0.65. CONCLUSIONS: According to the results it might be stated that both proton pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is more effective than pantoprazole as acid-supressor, with statistically significative differences. There was no difference between 20 mg omeprazole and 40 mg pantoprazole.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Benzimidazóis/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Gástrico , Omeprazol/farmacologia , Bombas de Próton/antagonistas & inibidores , Sulfóxidos/farmacologia , Análise de Variância , Benzimidazóis/administração & dosagem , Estudos Cross-Over , Inibidores Enzimáticos/administração & dosagem , Determinação da Acidez Gástrica , Concentração de Íons de Hidrogênio , Manometria , Omeprazol/administração & dosagem , Distribuição Aleatória , Sulfóxidos/administração & dosagem , Fatores de Tempo
9.
Acta gastroenterol. latinoam ; 33(4): 199-203, 2003. tab
Artigo em Espanhol | BINACIS | ID: bin-4798

RESUMO

OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24-h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0, basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then "wash out" for 7 days and thereafter 7 more days therapy with PZ or OZ. On day 22 a 24-h intragastric pH control was performed again. In the last treatment stage, all of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL 22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57 +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001. Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4) 0.65. CONCLUSIONS: According to the results it might be stated that both proton pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is more effective than pantoprazole as acid-supressor, with statistically significative differences. There was no difference between 20 mg omeprazole and 40 mg pantoprazole.(AU)


Assuntos
Estudo Comparativo , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Benzimidazóis/farmacologia , Omeprazol/farmacologia , Ácido Gástrico/metabolismo , Inibidores Enzimáticos/farmacologia , Bombas de Próton/antagonistas & inibidores , Sulfóxidos/farmacologia , Benzimidazóis/administração & dosagem , Omeprazol/administração & dosagem , Estudos Cross-Over , Concentração de Íons de Hidrogênio , Inibidores Enzimáticos/administração & dosagem , Fatores de Tempo , Determinação da Acidez Gástrica , Distribuição Aleatória , Análise de Variância , Manometria , Sulfóxidos/administração & dosagem
10.
Acta gastroenterol. latinoam ; 33(4): 199-203, 2003.
Artigo em Espanhol | BINACIS | ID: bin-38809

RESUMO

OBJECTIVE: To compare the acid-supressing capacity of omeprazole (OZ) 20 mg tablets vs pantoprazole (PZ) 20 and 40 mg tablets, in healthy volunteers, with 24-h intragastric pH-metry. MATERIAL AND METHODS: Open, randomized, cross-over trial in 10 healthy volunteers; on days 0.8 and 22, 24-h intragastric pH-metry. Day 0, basal, thereafter 7 days with OZ or PZ 20 mg/day; day 8, pH-metry, then [quot ]wash out[quot ] for 7 days and thereafter 7 more days therapy with PZ or OZ. On day 22 a 24-h intragastric pH control was performed again. In the last treatment stage, all of them were administered pantoprazole 40 mg/day for 8 days again with a 24-h pH recording at the end. RESULTS: 24-h pH-metry expressed as the time (hours) in which the pH was < or = 4 and the values as mean +/- standard deviation. BASAL 22.12 +/- 1.54, POST-OZ 9.78 +/- 6.72, POST-PZ 20 15.65 +/- 5.65, POST-PZ 40 8.57 +/- 5.93. Statistical evaluation with two way repeated measures ANOVA p < 0.0001. Newman Keuls post-hoc test: (1) vs (2) p < 0.003; (1) vs (3) p < 0.03; (2) vs (4) 0.65. CONCLUSIONS: According to the results it might be stated that both proton pump inhibitors have acid-supressing capacity and omeprazole in equal dosis is more effective than pantoprazole as acid-supressor, with statistically significative differences. There was no difference between 20 mg omeprazole and 40 mg pantoprazole.

11.
Acta gastroenterol. latinoam ; 32(2): 83-85, nov. 2002.
Artigo em Espanhol | LILACS | ID: lil-327728

RESUMO

Nowadays technics for Helicobacter pylori detection in stools like culture, and PCR, are expensive and difficult to perform. The aim of this study was to evaluate ELISA test efficacy for detection of H. Pylori antigens in stools comparing this results with standarized technics like histology (Giemsa), ureasa test and UBT C 14. 26 patients were evaluated in this study, ages between 15-75 with upper gastrointestinal symptoms; all of them required gastroduodenal endoscopy, status H. Pylori was determined with methods upon mentioned. 24 hours after endoscopy H. Pylori antigens in stools with the technique Premier Platinum Htsa, Elisa were determined. The detection of H. Pylori antigens in stools accurately identified active H. Pylori infection. The performance characteristics of this non-invasive method was similar in sensibility and specificity to conventional tests


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Antígenos de Bactérias , Fezes , Infecções por Helicobacter , Helicobacter pylori , Técnicas Imunoenzimáticas , Ensaio de Imunoadsorção Enzimática , Sensibilidade e Especificidade
12.
Acta gastroenterol. latinoam ; 32(2): 83-85, nov. 2002.
Artigo em Espanhol | BINACIS | ID: bin-7030

RESUMO

Nowadays technics for Helicobacter pylori detection in stools like culture, and PCR, are expensive and difficult to perform. The aim of this study was to evaluate ELISA test efficacy for detection of H. Pylori antigens in stools comparing this results with standarized technics like histology (Giemsa), ureasa test and UBT C 14. 26 patients were evaluated in this study, ages between 15-75 with upper gastrointestinal symptoms; all of them required gastroduodenal endoscopy, status H. Pylori was determined with methods upon mentioned. 24 hours after endoscopy H. Pylori antigens in stools with the technique Premier Platinum Htsa, Elisa were determined. The detection of H. Pylori antigens in stools accurately identified active H. Pylori infection. The performance characteristics of this non-invasive method was similar in sensibility and specificity to conventional tests (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Antígenos de Bactérias/análise , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/imunologia , Técnicas Imunoenzimáticas/métodos , Ensaio de Imunoadsorção Enzimática/normas , Sensibilidade e Especificidade
13.
Acta Gastroenterol Latinoam ; 32(2): 83-5, 2002.
Artigo em Espanhol | MEDLINE | ID: mdl-12553159

RESUMO

Nowadays technics for Helicobacter pylori detection in stools like culture, and PCR, are expensive and difficult to perform. The aim of this study was to evaluate ELISA test efficacy for detection of H. Pylori antigens in stools comparing this results with standarized technics like histology (Giemsa), ureasa test and UBT C 14. 26 patients were evaluated in this study, ages between 15-75 with upper gastrointestinal symptoms; all of them required gastroduodenal endoscopy, status H. Pylori was determined with methods upon mentioned. 24 hours after endoscopy H. Pylori antigens in stools with the technique Premier Platinum Htsa, Elisa were determined. The detection of H. Pylori antigens in stools accurately identified active H. Pylori infection. The performance characteristics of this non-invasive method was similar in sensibility and specificity to conventional tests.


Assuntos
Antígenos de Bactérias/análise , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/imunologia , Técnicas Imunoenzimáticas/métodos , Adolescente , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade
14.
Med Pediatr Oncol ; 36(1): 104-7, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11464857

RESUMO

BACKGROUND: The expression of several genes is modulated during neuroblastoma differentiation. The retinoblastoma family proteins, pRb, p107 and pRb2/p130, act in the repression of proliferation genes, interacting mainly with the E2F transcription factors. PROCEDURE AND RESULTS: In this study, we found that, in neuroblastoma cell lines, pRb and p107 proteins decreased, undergoing progressive dephosphorylation, whereas pRb2/p130 increased at late stages of differentiation. B-myb expression was down-regulated in association with the up-regulation of pRb2/p130, the major partner of E2F on the E2F site of the B-myb promoter in differentiated cells. Transfection of each of the retinoblastoma family genes in neuroblastoma cells was able to induce neural differentiation, to inhibit 3H-thymidine incorporation, and to down-regulate B-myb promoter activity. CONCLUSIONS: In conclusion, our data suggest a major contribution of retinoblastoma proteins, and especially of pRb2/p130, in B-myb promoter regulation and demonstrate the induction of neural differentiation by p107 and pRb2/p130, suggesting a role of these proteins in triggering differentiation-specific genes.


Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/biossíntese , Regulação Neoplásica da Expressão Gênica , Genes myb , Proteínas de Neoplasias/fisiologia , Neuroblastoma/genética , Proteínas Nucleares/fisiologia , Fosfoproteínas/fisiologia , Proteínas , Proteína do Retinoblastoma/fisiologia , Transativadores/biossíntese , Animais , Diferenciação Celular/efeitos dos fármacos , Dimetil Sulfóxido/farmacologia , Fatores de Transcrição E2F , Genes Reporter , Genes do Retinoblastoma , Humanos , Luciferases/biossíntese , Camundongos , Proteínas de Neoplasias/genética , Neuroblastoma/patologia , Proteínas Nucleares/genética , Fosfoproteínas/genética , Regiões Promotoras Genéticas , Proteínas Recombinantes de Fusão/biossíntese , Proteína p107 Retinoblastoma-Like , Proteína p130 Retinoblastoma-Like , Fatores de Transcrição/fisiologia , Transfecção , Tretinoína/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo
15.
Med Pediatr Oncol ; 36(1): 93-6, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11464913

RESUMO

BACKGROUND AND PROCEDURE: Nm23 gene family has been associated with metastasis suppression and differentiation. We studied DR-nm23 during neuroblastoma cells differentiation. DR-nm23 expression increased after retinoic acid induction of differentiation in human cell lines SK-N-SH and LAN-5. RESULTS: In several cell lines, overexpression of DR-nm23 was associated with more differentiated phenotypes. SK-N-SH cells increased vimentin expression, increased deposition of collagen type IV, modulated integrin expression, and underwent growth arrest; the murine neuroblastoma cell line N1E-115 showed neurite outgrowth and a striking enhancement of beta1 integrin expression. Up-regulation of beta1 integrin was specifically responsible for the increase in the adhesion to collagen type I-coated plates. Finally, cells overexpressing DR-nm23 were unable to growth in soft agar. CONCLUSIONS: In conclusion, DR-nm23 expression is directly involved in differentiation of neuroblastoma cells, and its ability to affects the adhesion to extracellular substrates and to inhibit growth in soft agar suggests an involvement in the metastatic potential of neuroblastoma.


Assuntos
Integrina beta1/biossíntese , Isoenzimas/fisiologia , Proteínas Monoméricas de Ligação ao GTP/fisiologia , Proteínas de Neoplasias/fisiologia , Neuroblastoma/patologia , Núcleosídeo-Difosfato Quinase/fisiologia , Fatores de Transcrição/fisiologia , Ágar , Animais , Adesão Celular , Diferenciação Celular , Colágeno/biossíntese , Colágeno/genética , Meios de Cultura , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina beta1/genética , Peptídeos e Proteínas de Sinalização Intracelular , Isoenzimas/biossíntese , Isoenzimas/genética , Camundongos , Proteínas Monoméricas de Ligação ao GTP/biossíntese , Proteínas Monoméricas de Ligação ao GTP/genética , Nucleosídeo NM23 Difosfato Quinases , Metástase Neoplásica , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neuritos/ultraestrutura , Neuroblastoma/enzimologia , Neuroblastoma/genética , Núcleosídeo-Difosfato Quinase/biossíntese , Núcleosídeo-Difosfato Quinase/genética , Fenótipo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/fisiologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Transfecção , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/metabolismo , Vimentina/biossíntese , Vimentina/genética
16.
Cell Death Differ ; 7(9): 843-50, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11042679

RESUMO

DR-nm23 belongs to a gene family which includes nm23-H1, originally identified as a candidate metastasis suppressor gene. Nm23 genes are expressed in different tumor types where their levels have been alternatively associated with reduced or increased metastatic potential. Nm23-H1, -H2, DR-nm23 and nm23-H4 all possess NDP kinase activity. Overexpression of DR-nm23 inhibits differentiation and promotes apoptosis in hematopoietic cells. By contrast, it induces morphological and biochemical changes associated with neural differentiation in neuroblastoma cells. In this study, we show that mutations in the catalytic domain and in the serine 61 phosphorylation site, possibly required for protein-protein interactions, impair the ability of DR-nm23 to induce neural differentiation. Moreover, neuroblastoma cells overexpressing wild-type or mutant DR-nm23 are less sensitive to apoptosis triggered by serum withdrawal. By subcellular fractionation, wild-type and mutant DR-nm23 localize in the cytoplasm and prevalently in the mitochondrial fraction. In co-immunoprecipitation experiments, wild-type DR-nm23 binds other members of nm23 family, but mutations in the catalytic and in the RGD domains and in serine 61 inhibit the formation of hetero-multimers. Thus, the integrity of the NDP kinase activity and the presence of a serine residue in position 61 seem essential for the ability of DR-nm23 to trigger differentiation and to bind other Nm23 proteins, but not for the anti-apoptotic effect in neuroblastoma cells. These studies underline the tissue specificity of the biological effects induced by DR-nm23 expression.


Assuntos
Apoptose , Diferenciação Celular , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Neuroblastoma/patologia , Neurônios/citologia , Núcleosídeo-Difosfato Quinase/metabolismo , Fatores de Transcrição/metabolismo , Animais , Domínio Catalítico , Diferenciação Celular/genética , Fracionamento Celular , Tamanho Celular , Meios de Cultura Livres de Soro , DNA Complementar/metabolismo , Genes Reporter , Genes myc , Immunoblotting , Marcação In Situ das Extremidades Cortadas , Camundongos , Proteínas Monoméricas de Ligação ao GTP/química , Proteínas Monoméricas de Ligação ao GTP/genética , Mutagênese Sítio-Dirigida , Nucleosídeo NM23 Difosfato Quinases , Neuroblastoma/enzimologia , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neurônios/metabolismo , Nucleosídeo Difosfato Quinase D , Fosforilação , Testes de Precipitina , Fatores de Transcrição/química , Fatores de Transcrição/genética , Transfecção , Células Tumorais Cultivadas
17.
Acta Gastroenterol Latinoam ; 29(4): 251-3, 1999.
Artigo em Espanhol | MEDLINE | ID: mdl-10599400

RESUMO

Some papers report helicobacter pylori existence in bile from surgical specimens obtained during gallbladder or bile ducts surgery. The aim of this work was search by PCR, H. Pylori presence in bile specimens from patients suffering of gallbladder stones or by bile ducts stones. Bile samples were obtained by gallbladder punction during cholecystectomy in 26 patients, 19 of them with gallbladder stones and 7 also with gallbladder stones and bile duct stones. Age ranged from 22-69 years old, median 49.6 years old. Samples were sent to specialized biomolecular laboratory to perform PCR techniques. Two of 26 patients (7.6%) had positive reaction for the presence of DNA of H. Pylori in bile samples. Our research suggest that DNA of H. Pylori can be founded in bile samples patients with gallbladders and duct stones in Argentina.


Assuntos
Colelitíase/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Adulto , Idoso , Doenças dos Ductos Biliares/microbiologia , DNA Bacteriano/análise , Humanos , Pessoa de Meia-Idade
18.
Cancer Res ; 59(14): 3365-8, 1999 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-10416595

RESUMO

The transcription factors of the Myb family are expressed in several tissues and play an important role in cell proliferation, differentiation, and survival In this study, the expression of A-myb, B-myb, and c-myb was investigated in a group of 64 neuroblastomas at different dinical stages by a sensitive reverse transcription-PCR tchnique and correlated with patients' survival. All of the myb genes were frequently expressed in neuroblastoma tumors. Interestingly, the expression of B-myb, which was detected in 33 cases, was associated with an increased risk of death (P = 0.027 in a univariate analysis), whereas there was no correlation with A-myb and c-myb expression. In addition, in a multivariate Cox regression analysis that included myb gene expression, MYCN status, age at diagnosis, and tumor staging, MYCN amplification and B-myb expression were independently associated to an increased risk (P < 0.01 and P = 0.015, respectively). In overall survival curves obtained by stratifying the neuroblastoma cases on the basis of MYCN status and B-myb expression, the group of patients without MYCN amplification and positive for B-myb expression had worse survival probability than that without MYCN amplification and nonexpressing B-myb (P < 0.01). In summary, these findings provide the first demonstration that B-myb expression can be a useful prognostic marker in human neuroblastoma. Moreover, B-myb expression has a prognostic value complementary to MYCN amplification and can identify a group of high-risk patients that would not be predicted on the basis of the MYCN status only.


Assuntos
Proteínas de Ciclo Celular , Proteínas de Ligação a DNA/biossíntese , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Genes myc , Neuroblastoma/genética , Oncogenes , Transativadores/biossíntese , Criança , Pré-Escolar , Seguimentos , Humanos , Lactente , Recém-Nascido , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Prognóstico , Modelos de Riscos Proporcionais , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida
19.
Acta gastroenterol. latinoam ; 29(4): 251-3, 1999.
Artigo em Espanhol | BINACIS | ID: bin-14377

RESUMO

Algunos trabajos describen la presencia de H. Pylori en muestras de bilis obtenidas durante la cirurgía por litiasis en vesícula y vías biliares. El objetivo de este trabajo, ha sido detectar la presencia del ADN del H. Pylori por medio de la Reacción en cadena de la Polimerasa (PCR) en muestras de bilis de pacientes con litasis vesicular y/o de vías biliares. Las muestras de bilis fueron obtenidas de 26 pacientes, 19 con litiasis vesicular y 7 con litiasis vesicular y coledociana, con edades comprendidas entre 22 a 69 años, media de 49,6 años, por punción de vesicular durante la colecistectomia. Las muestras fueron tratadas adecuadamente y preparadas para su investigación por PCR. 2 de 26 casos (7,6 por ciento) fueron positivos para la presencia en bilis del DNA del H. Pylori. Nuestro trabajo sugiere que el DNA del H P puede ser encontrado en muestras de bilis de pacientes portadores de litiasis biliar en la Argentina. (AU)


Assuntos
Humanos , Idoso , Pessoa de Meia-Idade , Adulto , Helicobacter pylori/isolamento & purificação , Colelitíase/microbiologia , Infecções por Helicobacter/microbiologia , Reação em Cadeia da Polimerase , Doenças dos Ductos Biliares/microbiologia , Colecistectomia , DNA Bacteriano/análise
20.
Acta gastroenterol. latinoam ; 29(4): 251-3, 1999.
Artigo em Espanhol | LILACS | ID: lil-248008

RESUMO

Algunos trabajos describen la presencia de H. Pylori en muestras de bilis obtenidas durante la cirurgía por litiasis en vesícula y vías biliares. El objetivo de este trabajo, ha sido detectar la presencia del ADN del H. Pylori por medio de la Reacción en cadena de la Polimerasa (PCR) en muestras de bilis de pacientes con litasis vesicular y/o de vías biliares. Las muestras de bilis fueron obtenidas de 26 pacientes, 19 con litiasis vesicular y 7 con litiasis vesicular y coledociana, con edades comprendidas entre 22 a 69 años, media de 49,6 años, por punción de vesicular durante la colecistectomia. Las muestras fueron tratadas adecuadamente y preparadas para su investigación por PCR. 2 de 26 casos (7,6 por ciento) fueron positivos para la presencia en bilis del DNA del H. Pylori. Nuestro trabajo sugiere que el DNA del H P puede ser encontrado en muestras de bilis de pacientes portadores de litiasis biliar en la Argentina.


Assuntos
Humanos , Idoso , Pessoa de Meia-Idade , Adulto , Colelitíase/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Doenças dos Ductos Biliares/microbiologia , Colecistectomia , DNA Bacteriano/análise , Reação em Cadeia da Polimerase
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